HETEROCYCLES

■ Contents

■ Carbonylative Palladium-Catalyzed Reactions of Lactam-, Lactone-, and Thiolactone-Derived Vinyl Triflates and Phosphates for the Synthesis of N-, O-, and S-Heterocycles

Ernesto G. Occhiato,* Dina Scarpi, and Cristina Prandi*

*Dipartimento di Chimica Organica “Ugo Schiff”, Università di Firenze, Via della Lastruccia n. 13, I-50019 Sesto Fiorentino (Fi), Italy

Abstract

A full account of our most recent studies on the chemistry of lactam-, lactone-, and thiolactone-derived vinyl triflates and phosphates is reported. In this review we focus on the use of these versatile electrophiles in Pd-catalyzed carbonylative reactions. They provide, through alkoxycarbonylation, aminocarbonylation and carbonylative Suzuki-Miyaura reactions, a straightforward and convenient access to useful intermediates for the synthesis of N-, O- and S-heterocyclic and natural compounds.

■ Recent Development for Formation of Aromatic Compounds via Metallacyclopentadienes as Metal-Containing Heterocycles

Lishan Zhou, Shi Li, Ken-ichiro Kanno, and Tamotsu Takahashi*

*Catalysis Research Center and Graduate School of Pharmaceutical Science, Hokkaido University, Sapporo 001-0021, Japan

Abstract

Metallacyclopentadiene, which is recognized as a metal-containing heterocycle, is an important intermediate for the formation of aromatic derivatives. In this short review, we summarized the recent advance in selective aromatic compounds formation catalyzed or mediated by transition metal complexes via metallacyclopentadienes which are formed by intermolecular coupling of various alkynes including unsymmetrical alkynes, two different alkynes and three different alkynes. Some reaction mechanisms were also reviewed.

■ Bioactive Cyclic Peptides from Higher Plants

Hiroshi Morita* and Koichi Takeya

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Cyclic peptides comprise a class of naturally occurring molecules, which exhibit a range of biological activities, and have attracted great interest from a biogenetic point of view as well as providing challenging targets for total synthesis. This review covered the structure elucidation and biological activity of cyclic peptides recently isolated from higher plants such as Amaranthaceae, Annonaceae, Caryophyllaceae, Compositae, Linaceae, Rutaceae, and Rubiaceae.

■ Enantioselective Synthesis of 2-Aryl-2,3-dihydro-4-quinolones by Chiral Brønsted Acid Catalyzed Intramolecular Aza-Michael Addition Reaction

Zhen Feng, Qing-Long Xu, Li-Xin Dai, and Shu-Li You*

*State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, 354 Finglin Road, Shanghai 200032, China

Abstract

Asymmetric intramolecular aza-Michael addition of activated α,β-unsaturated ketones catalyzed by chiral N-triflyl phosphoramide was realized. Enantioenriched 2-aryl-2,3-dihydroquinolin-4-ones can be obtained in excellent yields (77-98%) with up to 82% ee.

■ Facile Synthesis and Ring-Opening of 4-(Tributylstannyl)pyrrolidine-2-carboxylates

Makoto Shimizu,* Hiromi Ando, Hitoshi Shibuya, and Iwao Hachiya

*Department of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Tsu, Mie 514-8507, Japan

Abstract

On treatment of ethyl 2-(4-methoxyphenylimino)acetate with (E)-1-tert-butyldimethylsiloxy-3-tributylstannylalkenes in the presence of methanesulfonic acid (MsOH) at -78 °C, a ring-closing reaction proceeded to give 4-(tributylstannyl)pyrrolidine-2-carboxylates, while their ring-opening reaction was observed to give homoallylic amines under the influence of MsOH at -20 °C to room temperature.

■ Boron Trichloride Mediated Alkyne-Aldehyde Coupling Reactions

Min-Liang Yao, Michael P. Quinn, and George W. Kabalka*

*Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, Tennessee 37996-1600, U.S.A.

Abstract

The boron trichloride mediated reaction of aryl aldehydes and alkynes can be used to selectively generate either (Z,Z)- or (Z,E)-1,5-dichloro-1,4-dienes as major products, depending on the reaction conditions employed. To investigate the mechanism of this important carbon-carbon bond forming reaction, the boron trichloride mediated reaction of phenylacetylene with p-bromobenzaldehyde was chosen as the model system. Interestingly, when the coupling reactions are carried out below –60 °C, (E,E)-1,5-dichloro-1,4-dienes are also formed. The ratios of (Z,Z)-, (Z,E)-, and (E,E)-1,5-dichloro-1,4-dienes were correlated to the reaction conditions using gas chromatography-mass spectrometry. The results of the investigation can be used to explain why the ratio of (Z,E)-, (Z,Z)-, and (E,E)-1,5-dichloro-1,4-pentadiene products change very dramatically when changes are made in either the sequence of addition of the reagents or the reaction temperature.

■ Allylic Alkylation of Indoles with Butadiene Promoted by Palladium Catalyst and Triethylborane

Masanari Kimura,* Katsumi Tohyama, Yumi Yamaguchi, and Tomohiko Kohno

*Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

Triethylborane promotes the Pd-catalyzed allylic alkylation of a wide variety of indoles with 1,3-butadiene to provide C3-octadienylindoles and C3-bis(octadienyl)indolenines in good to excellent yields under mild conditions.

■ Organocatalytic Asymmetric Diels-Alder Reaction of Furan under High Pressure

Akiko Mimoto, Keiji Nakano, Yoshiyasu Ichikawa, and Hiyoshizo Kotsuki*

*Faculty of Science, Kochi University, 2-5-1, Akebono-cho, Kochi 780-8520, Japan

Abstract

A new method for the asymmetric Diels-Alder reaction between furan and acrolein has been developed through the combined use of chiral organocatalysts and high pressure (yield up to 91%; endo-adduct up to 19% ee, exo-adduct up to 26% ee).

■ Methyl Insertion Reactions of Tetrahydropyrans Having a C1’-Mesyloxy Group on the C2-Side Chain with Trimethylaluminum

Keigo Nakamura, Atsushi Kimishima, and Tadashi Nakata*

*Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan

Abstract

Methyl insertion reactions of tetrahydropyrans having a C1’-mesyloxy group on the C2-side chain, mediated by trimethylaluminum, were investigated. Removal of the mesyloxy group, 1,2-hydride shift and/or ring-expansion, and methyl insertion took place concertedly, depending on the stereostructure of the substrate, to give 2-methylated tetrahydropyran and/or 2- or 3-methylated oxepane.

■ Synthesis of the 1,2-Anti Type of 3E-Alkene-1,2,5-triol Derivatives

Yuichi Kobayashi,* Akira Takeuchi, and Hatsuhiko Hattori

*Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan

Abstract

We invented an efficient method to obtain 3E-alkene-1,2,5-triol derivatives with 1,2-anti stereochemistry from the 2Z,4E-alkadienyl alcohol derivatives, which were synthesized by using nickel-catalyzed coupling between lithium 1E-alkenyl borates and 1-halo-1Z-alken-3-ols. The method involves (1) asymmetric dihydroxylation at the E olefin moiety of the dienyl alcohol derivatives followed by formation of a cyclic carbonates; (2) palladium-catalyzed reaction with AcOH in the presence of Et3N. The method was applied successfully to the synthesis of the C6–C20 part of trioxilin A3.

■ Preparation and Photochemical Properties of [2]Rotaxanes Containing an Aniline Moiety Encapsulated by Crown Ethers

Yuji Tokunaga,* Satoshi Nakashima, Takuya Iwamoto, Kei Gambayashi, Kenji Hisada, and Tomonori Hoshi

*Department of Materials Science and Engineering, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910-8507, Japan

Abstract

This paper describes preparation of rotaxanes having an aniline moiety in the axle and crown ethers as wheels through an imine formation reaction and hydrogen-bond-guided self-assembly. UV-vis and emission measurements of the rotaxanes show that both absorption and fluorescence bands shift to longer wavelengths as compared to those of the unencapsulated axle component.

■ Synthesis of the ABC Ring Fragment of Brevisin, a New Dinoflagellate Polycyclic Ether

Naohito Ohtani, Ryosuke Tsutsumi, Takefumi Kuranaga, Tomohiro Shirai, Jeffrey L. C. Wright, Daniel G. Baden, Masayuki Satake,* and Kazuo Tachibana*

*Department of Chemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

A polycyclic ether, brevisin was isolated from the red-tide dinoflagellate Karenia brevis. Its unique skeletal structure consists of two separate tricyclic ether assemblies connected by a methylene bridge. The ABC ring fragment of brevisin was synthesized via Suzuki–Miyaura cross coupling toward a total synthesis of brevisin.

■ Nucleophilic Addition of Hetaryllithium Compounds to 3-Nitro-1-(phenylsulfonyl)indole: Synthesis of Tetracyclic Thieno[3,2-c]-δ-carbolines

Philip E. Alford, Tara L. S. Kishbaugh, and Gordon W. Gribble*

*Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover,
New Hampshire 03755, U.S.A.

Abstract

3-Nitro-1-(phenylsulfonyl)indole undergoes addition of aryl- and hetaryllithium nucleophiles to produce 2-substituted-3-nitroindoles. Mild reductive–acylation provides excellent access to 3-amido-2-hetarylindoles from which new thieno[3,2-c]-δ-carbolines are synthesized by cyclodehydration.

■ Divergent Synthesis of Lamellarin α 13-Sulfate, 20-Sulfate, and 13,20-Disulfate

Tsutomu Fukuda, Takeshi Ohta, Sho Saeki, and Masatomo Iwao*

*Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

A divergent synthesis of three sulfate derivatives of lamellarin α, namely, lamellarin α 13-sulfate (2), 20-sulfate (1), and 13,20-disulfate (4) has been achieved via a common intermediate (6) in which 13-OH and 20-OH of the lamellarin core are differentially protected by MOM and benzyl groups, respectively. Compound (6) in turn was prepared using sequential Suzuki-Miyaura coupling of 3,4-dihydroxypyrrole bistriflate (7) as a key reaction.

■ Diversity-Oriented Approach to 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid (Tic) Derivatives Using Diethyl Acetamidomalonate as a Glycine Equivalent: Further Expansion by Suzuki–Miyaura Cross-Coupling Reaction

Sambasivarao Kotha,* Shilpi Misra, Nimita Gopal Krishna, Nagaraju Devunuri, Henning Hopf, and Abhilash Keecherikunnel

*Department of Chemistry, Indian Institute of Technology, Powai, Mumbai 400 076, India

Abstract

Synthesis of diverse 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives and its higher analogues are reported using diethyl acetamidomalonate as a glycine equivalent. In addition, various substituted Tic derivatives are assembled by application of Suzuki−Miyaura cross-coupling reaction as a key step.

■ Oxidant-Free Lactonization of Diols Using a Hydrotalcite-Supported Copper Catalyst

Yusuke Mikami, Kaori Ebata, Takato Mitsudome, Tomoo Mizugaki, Koichiro Jitsukawa, and Kiyotomi Kaneda*

*Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan

Abstract

We newly synthesized well-crystallized hydrotalcite-supported copper nanoparticles, denoted as Cu/HT(c), which acted as a highly efficient heterogeneous catalyst for oxidant-free lactonization of various diols under liquid-phase conditions. The Cu/HT(c) catalyst could be recovered by simple filtration and reused without the significant loss of its activity and selectivity.

■ Synthesis of α-Alkylidene-δ-valerolactones via the Conjugate Addition of Ketone Enolates to Functionalized Allyl Acetates

P. Veeraraghavan Ramachandran* and Annyt Bhattacharyya

*Herbert C. Brown Center for Borane Research, Department of Chemistry, Purdue University, 560 Oval Dr.; BRWN 5131
West Lafayette, IN 47907-2084, U.S.A.

Abstract

Sequential addition of ketone enolates to allyl acetates bearing an ester, followed by reduction and cyclization provides a variety of substituted α-alkylidene-δ-valerolactones.

■ Synthesis of Zanthoxyline and Its Related Compounds: Revision of the Reported Structure

Hitoshi Abe,* Naoko Kobayashi, Yasuo Takeuchi, and Takashi Harayama*

*Department of Applied Chemistry, Faculty of Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

Benzo[c]phenanthridine alkaloid, zanthoxyline, was synthesized through an intramolecular biaryl coupling reaction of N-naphthylbenzamide derivative using a palladium reagent. Comparison of the NMR data for the synthetic product with that reported previously revealed that the proposed structure was incorrect. Synthesis of the related compounds suggested that the correct structure of zanthoxyline is the previously known decarine.

■ Novel Radical Cyclization Method Accompanied by Elimination of Hydrazyl Radical

Shoji Kobayashi, Hidefumi Hirao, Tatsuro Kawauchi, and Ilhyong Ryu*

*Department of Chemistry, Graduate School of Science, University of Osaka Prefecture, Sakai, Osaka 593-8531, Japan

Abstract

The potential of hydrazine group as the new radical leaving group was studied. Radical cyclization of (E)-1,1-dialkyl-2-(1-alkyloct-2-en-7-ynyl)hydrazines with n-Bu3SnH/AIBN, followed by protodestannylation, gave 1-alkenyl-2-methylenecyclopentanes, which arose by 5-exo cyclization and subsequent β-elimination of hydrazyl radical.

■ Catalytic Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Imines to Allyl Alcohol Utilizing Tartaric Acid Ester as a Chiral Auxiliary

Katsuyoshi Tanaka, Tomomitsu Kato, Yutaka Ukaji,* and Katsuhiko Inomata*

*Chemistry Course, College of Science and Engineering, School of Chemistry, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

The catalytic regio- and enantioselective 1,3-dipolar cycloaddition of azomethine imines to allyl alcohol was achieved by utilizing diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding optically active trans-pyrazolidines with enantioselectivities up to 93% ee. Addition of MgBr2 was crucial to realize reproducible high enantioselectivity.

■ Observation of 2,7-Disubstitution in Palladium Catalysed Directed C-H Activation of Indoles

Guilia Fanton, Nicola M. Coles, Andrew R. Cowley, Jonathan P. Flemming, and John M. Brown*

*Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.

Abstract

In previous work, controlled C-H activation and catalytic Heck reaction at the 2-position of indole was demonstrated. This was achieved by means of a N-(2-pyridylmethyl) directing group. In the course of extending the initial observations it was discovered that the corresponding N-(1-isoquinolylmethyl)indole derivative was prone to a further oxidative Heck reaction giving rise to a 2,7-disubstituted product, which was characterised by NMR and X-ray analysis. The parent pyridine showed no tendency for a second substitution reaction at the indole 7-position, but the related N-(2-quinolylmethyl) derivative did. In the case of the corresponding 6-methylphenanthridinyl derivative, a novel oxidative C-C cleavage reaction was observed.

■ Synthetic Studies toward Antitumor Sesquiterpenoid Quadrone

Akihiro Ishihata, Megumi Saeki, Masaru Watanabe, Masataka Ihara, and Masahiro Toyota*

*Department of Chemistry, Graduate School of Science, University of Osaka Prefecture, Sakai, Osaka 593-8531, Japan

Abstract

A palladium-catalyzed cycloalkenylation and an acid-promoted intramolecular Michael reaction were utilized as the key steps in a synthetic approach to sesquiterpene quadrone 1. This route capitalizes upon the ability of the above reactions to stereoselectively assemble tricyclic core 15 of quadrone 1.

■ Synthesis and π-Amphoteric Properties of Tris(tetrathiafulvaleno)hexadehydro[12]annulene

Kenji Hara, Masashi Hasegawa, Yoshiyuki Kuwatani, Hideo Enozawa, and Masahiko Iyoda*

*Graduate School of Science, Tokyo Metropolitan University, 1-1, Minami-ohsawa, Hachioji, Tokyo 192-0364, Japan

Abstract

The Sonogashira coupling reaction of the diiodide 6 of 1,2-[4,5-bis(butylthio)tetrathiafulvalenyl]ethyne with 4,5-bis(ethynyl)-4’,5’-bis(butylthio)tetrathiafulvanene 5 produced the corresponding tris(tetrathiafulvaleno)hexadehydro[12]annulene 1 in moderate yield. The [12]annulene 1 exhibits multi-redox behavior and solvatochromism in the neutral state.

■ Synthesis of Substituted Isoquinolines via Nickel-Catalyzed [2+2+2] Cycloaddition of Alkynes and 3,4-Pyridynes

Toshihiko Iwayama and Yoshihiro Sato*

*Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

A novel methodology for the synthesis of substituted isoquinolines via a nickel(0)-catalyzed [2+2+2] cycloaddition of 3,4-pyridynes with two molecules of alkyne has been established. In this reaction, it was found that 2-butyn-1,4-diol derivatives and 1,3-diynes are suitable as substrates and that a propargylic oxygen functionality in alkynes is essential for the reactivity and the selectivity of the products.

■ Water-Soluble Palladium and Gold Nanoparticles Functionalized by a New Phosphine with Zwitterionic Liquid Based on Imidazolium Sulfonate Linked Ethylene Glycol Moiety

Taichi Akiyama, Chiharu Ibata, and Hisashi Fujihara*

*Department of Applied Chemistry, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan

Abstract

A new phosphine with zwitterionic liquid based on imidazolium sulfonate linked ethylene glycol moiety (1) as a protective ligand for metal nanoparticles has been prepared. Its phosphine 1-stabilized palladium and gold nanoparticles (1-Pd and 1-Au) were found to be soluble in water, and remarkably stable in high concentration of aqueous electrolyte and ionic liquid. 1-Pd nanoparticles behave as an efficient catalyst for the Suzuki cross-coupling reaction in an aqueous medium.

■ Helical Chirality Control of Tropos Sandwich-Shaped L2M3 Complexes with C3-Symmetric Tris(diphenylphosphinophenyl)benzene Ligand

Kazuki Wakabayashi and Koichi Mikami*

*Department of Applied Chemistry, Graduate School of Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8552, Japan

Abstract

The L2M3 complexes with tropos C3-symmetric ligands interconvert rapidly between the chiral propeller (P)- and (M)-helicity of the sandwich-shaped L2M3 complexes at room temperature and are chirally controlled to adopt a single helical structure upon complexation with a chiral diamine. The L2M3 complexes chirally controlled can be employed for asymmetric transfer hydrogenation.

■ A Simple and Convenient High Yielding Synthesis of Substituted Isoindolines

Keith Smith,* Gamal A. El-Hiti, Amany S. Hegazy, and Ahmed Fekri

*School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, U.K.

Abstract

Trifluoroacetic anhydride-induced dehydration of substituted 2-(pivaloylaminomethyl)phenyl- and 2-(dimethylaminocarbonylmethyl)phenylmethanols gives the corresponding isoindolines in excellent yields when there are aryl substituents at the methanol carbon atom.

■ Synthesis of Polyazamacrocycles Comprising 6,6’-Diamino-2,2’-bipyridine Moieties via Pd-Catalyzed Amination

Alexei D. Averin,* Alexei N. Uglov, Alexei K. Buryak, Alla G. Bessmertnykh, Roger Guilard, and Irina P. Beletskaya*

*Department of Chemistry, Moscow State University, Leninskie Gory 1/3, 119991, Moscow, Russia

Abstract

Pd-catalyzed amination of 6,6’-dibromo-2,2’-bipyridine with a variety of di-, tri-, tetraamines and oxadiamines was carried out for the synthesis of a new class of polyazamacrocycles comprising a 6,6’-diamino-2,2’-bipyridine unit. The obtained results of the catalytic amination reaction were shown to be dramatically dependent on the nature of the amines, mainly on the length of the amine chain. The shortest propane-1,3-diamine and butane-1,4-diamine derivatives provided only cyclic dimers whereas the longest di- and trioxadiamines gave desired macrocycles in very good yields. The formation of cyclic oligomers was observed in all cases. Different reaction conditions leading to cyclic dimers were explored.

■ Utilization of the Suzuki Coupling to Enhance the Antituberculosis Activity of Aryloxazoles

Garrett C. Moraski, Scott G. Franzblau, and Marvin J. Miller*

*Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46656, U.S.A.

Abstract

Potent antituberculosis aryl oxazoles can be made in an efficient three step process--formation of β-hydroxy amides with serine benzyl ester; cyclization to afford oxazolines; and then dehydration to give the corresponding oxazoles. Furthermore, incorporation of an appropriate aryl halide allows utilization of the Suzuki cross coupling reaction to access new chemical space and more elaborate analogs. The compounds prepared by this method were shown to possess improved activity against M. tuberculosis, extremely low toxicity toward VERO cells and, as a result, high therapeutic indexes.